Dengue virus causes dengue fever, a debilitating illness marked by high fever, headache, muscle and joint pain, and rash. The more severe forms of the illness, dengue hemorrhagic fever and dengue shock syndrome, are life threatening and are a principal cause of hospitalization among children in Southeast Asia. Globally, the four serotypes of dengue are responsible for up to lOO million infections annually, and with the introduction of the Aedes albopictus vector mosquito to North America, dengue now poses a threat to the mainland United States. - The long range goal of the proposed research is to develop a safe and effective subunit vaccine against dengue infection. The Phase I research will test the feasibility of expressing dengue structural proteins in a Drosophila cell culture system and examine their association in a lipoprotein particle. Coexpression of the two membrane-anchored structural proteins of a related flavivirus have been shown to yield highly immunogenic proteins with native conformations in a particle; and the Drosophila cell expression system has expressed high levels (30 mg/L) of recombinant HIV gpl2O with biological properties indistinguishable from viral gpl20. High level Drosophila cell expression of dengue proteins in a lipoprotein particle form could lead to development of a successful tetravalent dengue subunit vaccine.